The extreme complexity of the nervous system relates to the diversity of neurons and their vast synaptic interconnections. The mechanisms by which neurons communicate with one another at these synapses, which almost always involve chemical neurotransmitter substances, are basic to the overall function of the system. Although an understanding of the chemistry of synapses is essential to rational treatment of many chemically-based derangements of the nervous system, progress in this area has lagged behind anatomical and physiological advances. This proposal constitutes a step in our long-range effort to understand the synaptic chemistry of one specific region of the brain which is well-defined in terms of its general composition and function: the cochlear nucleus of the auditory system. The cochlear nucleus presents a particulary favorable region for studies of synaptic mechanisms because of its advantageous situation for well-controlled physiological and anatomical studies. The basic methods for our approach to synaptic chemistry are those of quantitative histochemistry, by which quantitative chemical data can be obtained for tissue samples as small as 20 Mum in linear dimension. Careful mapping of sample locations facilitates correlation of data with anatomical and physiological results. The synaptic chemistry of a region may be approached by a search for the transmitter involved at a particular prominent synapse, or by a search for the synapses at which a particular prominent neurotransmitter is involved. We propose to take the latter approach in order to seek a solid foothold into the synaptic chemistry of the cochlear nucleus. Acetylcholine, which is probably the best established neurotransmitter substance, is likely to function at some synapses in the cochlear nucleus. We hope to help identify those synapses by mapping the depletion of acetylcholine-related enzyme activities distal to lesions of nerve pathways. Of the acetylcholine-related enzymes, choline acetyltransferase and acetylcholinesterase, the former will be emphasized as the more definitive marker.